Hydrochloric Acid → 2-Fluoro-4-phenylbenzoic acid

HRID 2053694Notes

Reaction equation

HRID 2053694 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[F:17])=[O:4].[OH-].[Na+].Cl>C1COCC1>[F:17][C:6]1[CH:7]=[C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:9]=[CH:10][C:5]=1[C:3]([OH:4])=[O:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69129634Methyl 2-fluoro-4-phenylbenzoate

Product 1

HCID 113902902-Fluoro-4-phenylbenzoic acidYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Combine methyl 2-fluoro-4-bromobenzoate (1.25 g, 5.36 mmol), phenylboronic acid (1.30 g, 10.72 mmol) and CsF (2.02 g, 13.40 mmol) in DMF (25 mL) and water (3.0 mL) with stirring. Place the hetereogeneous reaction mixture open to the air in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (120 mg, 0.536 mmol) in one portion and stir until reaction turns black. Cool reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash organics with water, dry over MgSO4, filter and evaporate. Purification by flash column chromatography yields 3-fluorobiphenyl-4-carboxylic acid methyl ester as a solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1 M NaOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 965 mg (84%) of the title compound. MS (m/e): 214.9 (M−).

Workup

  1. extractionextract with ethyl acetate
  2. customEvaporation of the solvent

Sources & evidence

ORD record
ord-5ac562ed753d48799069e9230ea9f11b
Source dataset
uspto-grants-2008_02
Patent number
US07326731B2

Reaction notes

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